SV40 vectors carrying minimal sequence of viral origin with exchangeable capsids

Nakanishi, Akira; Chapellier, Benoît; Maekawa, Naoya; Hara, Masaki; Kuge, Takeshi; Takahashi, Ryou U.; Handa, Hiroshi; Imai, Takeshi

doi:10.1016/j.virol.2008.06.032

Cited by 18 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on initial phylogenetic analyses, we chose BKV representatives from each of the major branches of the tree, specifically BKV-Ia (isolate name BK-D; accession number JF894228), BKV-Ib1 (KOM-5; AB211374) (15), BKV-Ib2 (PittVR2; DQ989796) (16), BKV-Ic (RYU-2; AB211377) (15), BKV-II (GBR-12; AB263920) (17), BKV-III (KOM-3; AB211386) (15), BKV-IVb1 (THK-8; AB211390) (15), and BKV-IVc2 (A-66H; AB369093) (2,9). A codonmodified version of the VP1 gene of each variant was designed according to a previously reported algorithm (18), with the exception of variant KOM-5, which was expressed from an unmodified late region fragment that includes the native agnoprotein and VP2/3 genes (19). The KOM-5 isolate encodes a VP1 protein sequence identical to that of the laboratory strain BK-D.…”

Section: Methodsmentioning

confidence: 99%

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Pastrana

Ray

Magaldi

et al. 2013

J Virol

View full text Add to dashboard Cite

BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. BK polyomaviruses (BKVs or BKPyVs) are a species of icosahedral, nonenveloped, double-stranded DNA viruses. The genomes of all known full-length isolates of BKV can be categorized into four discrete genotypes based on analyses of nucleotide sequences (1). The prevalence and sequence characteristics of each genotype are thought to vary within different human populations worldwide (2).Studies indicate that 83 to 98% of individuals show serum antibody responses to the BKV genotype I (BKV-I) major capsid protein, VP1, by the time they are 21 years of age (3). The virus is thought to establish a lifelong chronic infection in the urinary epithelium, and virions are periodically shed at low levels in the urine of 5 to 27% of healthy adults (4, 5). Although BKV-I can cause malignancy in animal model systems, conclusive evidence showing a causal connection between BKVs and human cancer is still lacking (reviewed in reference 6). While it remains uncertain whether BKVs cause pathology in healthy individuals, it is clear that certain T cell-immunosuppressed individuals, such as recipients of kidney or bone marrow transplants, are at risk of developing uncontrolled BKV replication that leads to nephropathy or hemorrhagic cystitis, respectively (reviewed in reference 7). Currently available antiv...

show abstract

Section: Methodsmentioning

confidence: 99%

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Pastrana

Ray

Magaldi

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…Furthermore, we could demonstrate this broad binding also to additional VP1 variants with mutations located within the exterior loops (for example, VP1 N74S , VP1 R75K , and VP1 T117S ) by using a complementary approach with pCAG-JCPyV–transfected cells (38) combined with intracellular staining and flow cytometry (fig. S2).…”

Section: Resultsmentioning

confidence: 96%

Broadly neutralizing human monoclonal JC polyomavirus VP1–specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy

et al. 2015

View full text Add to dashboard Cite

In immunocompromised individuals, JC polyomavirus (JCPyV) may mutate and gain access to the central nervous system resulting in progressive multifocal leukoencephalopathy (PML), an often fatal opportunistic infection for which no treatments are currently available. Despite recent progress, the contribution of JCPyV-specific humoral immunity to controlling asymptomatic infection throughout life and to eliminating JCPyV from the brain is poorly understood. We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti-VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show “recognition holes”; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell repertoire of individuals who recovered from PML could be a source for the molecular cloning of broadly neutralizing antibodies for passive immunization. We generated a series of memory B cell-derived JCPyV VP1-specific human monoclonal antibodies from HDs and a patient with NAT-associated PML-immune reconstitution inflammatory syndrome (IRIS). These antibodies exhibited diverse binding affinity, cross-reactivity with the closely related BK polyomavirus, recognition of PML-causing VP1 variants, and JCPyV neutralization. Almost all antibodies with exquisite specificity for JCPyV, neutralizing activity, recognition of all tested JCPyV PML variants, and high affinity were derived from one patient who had recovered from PML. These antibodies are promising drug candidates for the development of a treatment of PML.

show abstract

“…It has recently become possible to generate reporter vectors (also known as pseudoviruses) based on BKVs [35], [36]. These recombinant production systems made it possible for us to generate infectious capsids composed of the VP1/2/3 capsid proteins of BKV primary isolates of genotypes I and IV that are not otherwise culturable.…”

Section: Resultsmentioning

confidence: 99%

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

et al. 2012

View full text Add to dashboard Cite

BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.

show abstract

SV40 vectors carrying minimal sequence of viral origin with exchangeable capsids

Cited by 18 publications

References 40 publications

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

Broadly neutralizing human monoclonal JC polyomavirus VP1–specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy

Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

Contact Info

Product

Resources

About